Incidence of herpes zoster amongst adults varies by severity of immunosuppression

doi:10.1016/j.jinf.2017.06.010

Journal of Infection

Volume 75, Issue 3, September 2017, Pages 207-215

https://doi.org/10.1016/j.jinf.2017.06.010 Get rights and content

Highlights

•
The herpes zoster incidence is almost twice as high in immunocompromised patients than in immunocompetent individuals.
•
The herpes zoster incidence is highest in severely immunocompromised patients.
•
The prevalence of complications and of healthcare resource utilisations is highest in severely immunocompromised patients.

Summary

Objectives

We examined the incidence of herpes zoster in immunocompromised adults (≥18 years) with different severities of immunosuppression and assessed the prevalence of complications and of various kinds of healthcare resource utilisation.

Methods

German claims data from more than ten million adults were used to calculate annual incidence rates of herpes zoster for the years 2006–2012 and to analyse the prevalence of complications, physician visits, hospitalisations, and antiviral and analgesic treatments using a cohort design. The analyses were stratified by age, sex, and severity of immunosuppression, defined by immunocompromising conditions and drug therapies.

Results

The incidence rate per 1000 person-years of herpes zoster was almost twice as high in immunocompromised patients (11.5 (95% confidence interval (CI): 11.4–11.6)) compared to immunocompetent subjects (5.9 (95% CI: 5.8–5.9)). The incidence rate was higher in highly immunocompromised patients (13.4 (95% CI: 13.2–13.6)) than in patients with a low severity of immunosuppression (10.0 (95% CI: 9.8–10.1)). These differences were observed for both sexes and in all age groups. Complications, outpatient physician visits, hospitalisations, and analgesic treatments occurred more frequently in immunocompromised patients as well.

Conclusions

Our results show that immunocompromised individuals are affected by the disease in particular and that the burden of herpes zoster is highest in severely immunocompromised patients.

Introduction

Infection with the varicella zoster virus (VZV) usually occurs during infancy, causing chickenpox.¹ Decades later, the latent virus can be reactivated and result in herpes zoster (HZ) which is usually characterised by a painful skin rash.² Since the reactivation of the VZV is typically associated with a decline in cell-mediated immunity, older and immunocompromised (IC) individuals are at higher risk of developing HZ and its complications like postherpetic neuralgia (PHN) and VZV vasculopathy.2, 3, 4, 5, 6, 7, 8, 9 Accordingly, a recently published systematic review reported an HZ incidence rate (IR) between 6 and 8 per 1000 person-years (py) in 60-year-olds and between 8 and 12 per 1000 py at age 80.¹⁰ Studies also observed much higher IRs in IC individuals.11, 12, 13 Weitzman et al.,¹¹ for example, observed an HZ IR of 12.8 per 1000 py in IC subjects as compared to 3.5 per 1000 py in the total population. In a large study based on German health insurance data, Hillebrand et al.¹² found an HZ IR about 75% higher in IC patients than in immunocompetent ones.

While the epidemiology of HZ is generally well understood, data on the burden in different IC populations is more limited. So far, studies assessed the HZ incidence for single IC conditions5, 14, 15 or distinguished between the general population or immunocompetent individuals and IC patients12, 16, 17 but there was no further differentiation between different severities of immunosuppression. Such data is essential, however, since populations with different severities of immunosuppression may require different prevention strategies. This is for example the case with regard to vaccination where the currently available attenuated vaccine cannot be used in severely IC patients.

Therefore, the aim of this study was to estimate the incidence of HZ in a representative sample of German adults with different severities of immunosuppression. Besides, we assessed the prevalence of HZ complications and different aspects of healthcare resource utilisation in these populations.

Section snippets

Data source

The German Pharmacoepidemiological Research Database (GePaRD), which consists of claims data from four statutory health insurances (SHIs), was used for this study. At the time of the study's inception, GePaRD contained information on demographics, outpatient prescriptions, hospitalisations, and diagnoses for the years 2004–2012.¹⁸ In the database, diagnoses are coded according to the International Classification of Diseases, 10th Version, German Modification (ICD-10-GM). Outpatient data include

Study population

The annual study cohorts included a minimum of 9,554,821 (in 2008) and a maximum of 10,193,093 (in 2012) adult individuals with a higher share of women (55.1–56.7%). Between 2006 and 2012, the median age increased from 49 to 51 years. Table 2 shows the characteristics of the cohorts exemplarily for the first and the last study year. During the study period, the proportion of subjects in the study population categorised as IC increased from 25.5 to 34.0%.

Incidence of herpes zoster

The overall HZ IR varied between 6.76

Discussion

Our results showed an incidence of HZ about twice as high in IC than in immunocompetent subjects and higher incidences with increasing severity of immunosuppression. Besides, we observed higher incidences among women and in the older age groups. Among HZ patients, the prevalences of complications, concomitant diseases, hospitalisations, and treatments with pain medication increased with increasing severity of immunosuppression.

The higher HZ incidence among women is in accordance with studies

Conclusions

We were able to examine, for the first time in Germany, the burden of HZ in adults with different severities of immunosuppression. With decreasing immune status, we observed higher incidences of HZ and higher prevalences of complications and healthcare resource utilisations. This indicates that IC patients are particularly affected by the disease and that the burden is highest in severely IC patients. Our findings make it possible to estimate the number of people with different severities of

Funding

This study was funded by GlaxoSmithKline Biologicals S.A. (Rixensart, Belgium – e-track number: 201269) who had no further role in the conduct of the study, the collection, management, analysis, and interpretation of data, and the preparation, review, and approval of the manuscript.

Conflict of interest

C.S., D.E., T.S., and O.R. are working in departments that occasionally perform studies for pharmaceutical companies. These companies include Bayer, Celgene, GlaxoSmithKline, Mundipharma, Novartis, Sanofi, Sanofi Pasteur MSD, and STADA.

Acknowledgements

The authors would like to thank all statutory health insurance providers which provided data for this study, namely the AOK Bremen/Bremerhaven, the DAK-Gesundheit, the hkk Krankenkasse, and the Techniker Krankenkasse (TK).

The authors would also like to thank Dr. Heike Gerds for proofreading the final manuscript.

References (37)

G. Gross et al.
Herpes zoster guideline of the German Dermatology Society (DDG)
J Clin Virol
(2003)
D. Weitzman et al.
A population based study of the epidemiology of herpes zoster and its complications
J Infect
(2013)
K. Hillebrand et al.
Incidence of herpes zoster and its complications in Germany, 2005–2009
J Infect
(2015)
G. Mick et al.
[Burden of herpes zoster and postherpetic neuralgia: incidence, proportion, and associated costs in the French population aged 50 or over]
Revue d'épidémiologie et de santé publique
(2010)
S. Schneeweiss et al.
A review of uses of health care utilization databases for epidemiologic research on therapeutics
J Clin Epidemiol
(2005)
E. Miller et al.
Epidemiology, outcome and control of varicella-zoster infection
Rev Med Microbiol
(1993)
Robert Koch Institute
[Guidebook infectious diseases. Part 20: varicella, herpes zoster]
(2000)
M. Wittek et al.
Varicella and herpes zoster. Part 1: virology, epidemiology, clinical picture, laboratory diagnostics
Med Klin
(2010)
L.A. Habel et al.
The epidemiology of herpes zoster in patients with newly diagnosed cancer
Cancer Epidemiol Biomarkers Prev
(2013)
T.N. Tran et al.
Complications of herpes zoster in cancer patients
Scand J Infect Dis
(2014)

T. Schink et al.

Risk of stroke after herpes zoster – evidence from a German self-controlled case-series study

PLoS One

(2016)

B. Ultsch et al.

Herpes zoster in Germany: quantifying the burden of disease

BMC Infect Dis

(2011)

B. Ultsch et al.

Epidemiology and cost of herpes zoster and postherpetic neuralgia in Germany

Eur J Health Econ

(2013)

K. Kawai et al.

Systematic review of incidence and complications of herpes zoster: towards a global perspective

BMJ Open

(2014)

R.P. Insinga et al.

The incidence of herpes zoster in a United States administrative database

J General Intern Med

(2005)

A.P. Guignard et al.

Risk of herpes zoster among diabetics: a matched cohort study in a US insurance claim database before introduction of vaccination, 1997–2006

Infection

(2014)

S. Grabar et al.

Incidence of herpes zoster in HIV-infected adults in the combined antiretroviral therapy era: results from the FHDH-ANRS CO4 cohort

Clin Infect Dis

(2015)

H.J. Forbes et al.

Quantification of risk factors for herpes zoster: population based case-control study

BMJ

(2014)

Cited by (33)

Extraction, purification, structural characterization and biological activity of polysaccharides from Fritillaria: A review
2023, International Journal of Biological Macromolecules
Fritillaria is a traditional Chinese medicine(TCM) with a history of thousands of years. Fritillaria always contain saponins, alkaloids, amino acids, flavones, and polysaccharides. Among them, Fritillaria polysaccharide has a variety of biological activities. Its anti-inflammatory and antiaging activities are new study hotspots. The extraction, purification, quantitative determination, monosaccharide composition, and biological activity of Fritillaria polysaccharides have been examined for several years in an attempt to identify the active components and understand the pharmacological process. In this review, ample original publications related to the distribution, extraction, purification, quantitative determination, monosaccharide composition and biological activities of Fritillaria until 2023 were searched and collected by using various literature databases. Databases included the China National Knowledge Infrastructure, VIP database, Wan Fang database, PubMed, Elsevier, Springer, Science Direct, Google Scholar and Web of Science database, as well as the classic Chinese medical books and PhD and MSc theses. The properties and outcomes of various extractions, purifications, quantitative determination methods, monosaccharide compositions, and biological activities of Fritillaria polysaccharides are discussed here. Additionally, we summarize the research potential of Fritillaria polysaccharide and identify promising research direction candidates.
Patterns of use of recombinant zoster vaccine among commercially-insured immunocompetent and immunocompromised adults 50–64 years old in the United States
2023, Vaccine
Citation Excerpt :
Among the general U.S. population, the annual incidence rate of HZ is approximately 3.2/1,000 person-years. The risk of HZ among immunocompromised individuals is considerably higher than immunocompetent individuals, ranging from 7.8 to 20 cases per 1,000 person-years in studies using insurance claims data. [7–9] This is primarily a result of decreased T cell immunity leading to reactivation of the latent varicella zoster virus. [10]
The Centers for Disease Control and Prevention (CDC) recommends recombinant zoster vaccination (RZV) for adults ≥ 50 years to prevent herpes zoster (HZ) and its sequelae. Initially, no distinct recommendation was made for immunocompromised adults, who experience higher HZ rates and more severe outcomes. We characterized receipt of first RZV dose (initiation) and both doses (completion) over time, and the impact of immune function on RZV uptake among adults aged 50–64 years in the United States.
We identified RZV claims from the IBM MarketScan database between 1/1/2018 and 12/31/2019. We characterized immunocompromised enrollees as having malignancy, HIV, solid organ transplant, primary immunosuppression, or medication-induced immunosuppression using inpatient, outpatient, and prescription claims in the 6 months prior to study start. We evaluated patterns of vaccine uptake by demographic and healthcare access characteristics and immune status.
The cumulative incidence of RZV initiation during the study period was 10.0%. Incidence increased with age and number of medical office visits, and was higher among women, urban residents, high-deductible insurance beneficiaries, and those who were immunocompromised compared to immunocompetent. Among immunocompromised adults, RZV initiation was highest among those with HIV and primary immunodeficiencies. Of those who initiated RZV, 89.5% received both doses. RZV completion was highest among those who received the first dose at a pharmacy. Most enrollees (88.6%) who completed RZV vaccination did so within the recommended dosing schedule.
RZV uptake was low in the two years since the CDC recommendation, and differed by demographic, healthcare access, and clinical characteristics. Initiation rates were higher among immunocompromised adults compared to immunocompetent adults, despite no CDC recommendation for vaccination in these groups during the study period. The CDC has since recommended RZV for immunocompromised individuals, and our findings may inform efforts to increase RZV uptake in individuals at higher risk of severe disease.
Incidence and economic burden of herpes zoster and its complications in immunocompromised adults: a retrospective cohort study in an eastern county, China
2022, Journal of Infection
Incidence of complications of herpes zoster in individuals on immunosuppressive therapy: A register-based population study
2022, Journal of Infection
Citation Excerpt :
In this observational 13-year retrospective analysis from a claims database, adult individuals exposed to immunosuppressive therapy were three times more prone to complicated zoster compared to non-exposed individuals. Although HZ is more frequent with age and immunosuppression, its complications (i.e. PHN and/or hospitalization) in immunosuppressed individuals remain poorly evaluated 8,10,14,20,21,24-30. In our analysis, we observed that CZ was three times more frequent in EI than NEI, despite a similar sex ratio and age.
Herpes zoster (HZ) exposes to alterations of the quality-of-life. HZ is more frequent in immunocompromised individuals, but whether immunosuppression is associated with a higher rate of complications is not well documented. We aimed to assess association between drug-induced immunosuppression and HZ complications.
Data from a sample of the French healthcare claims from 01/01/2006 to 12/31/2018 were analyzed. Complicated zoster (CZ) was defined as a hospitalization with a code for HZ or the first-time dispensation of high-dose valacyclovir and specific neuralgia analgesics. Drug-induced immunosuppression was identified through medication dispensation. Risk ratios were calculated to compare incidences in exposed individuals (EI) and non-exposed to immunosuppressive therapy (NEI).
We identified 227 and 2838 CZ, accounting for an incidence of 178 per 100,000 person-year (95%CI[154.9–201.1]) and 51.7 per 100,000 person-year (95%CI[49.8–53.6]), in EI and NEI, respectively (risk ratio: 3.44 (95%CI[3.01–3.94]). Mean age was 66 years in both groups. CZ occurred after a median of 11.7 months (IQR[5.3–49.9]) of immunosuppressive therapy. Post-herpetic neuralgia (PHN) lasted at least 3 months in 32.6% and 22.5% of cases in EI and NEI, respectively (p=.01).
Drug-induced immunosuppression increases the risk of CZ and exposes to longer-lasting PHN. Figures provided in this study could help guide prophylaxis of HZ.
Violaceous ulcerated plaque in an immunocompromised patient. Diagnosis and comment
2020, Piel
Varicella-zoster virus post-exposure management and prophylaxis: A review
2019, Preventive Medicine Reports
Citation Excerpt :
The reasons underlying shifting patterns of HZ incidence among adults are unknown but appear unrelated to widespread varicella vaccination of children given that HZ incidence began increasing before introduction of varicella vaccine and did not increase more rapidly after routine immunization against varicella began (Hales et al., 2013; Kawai et al., 2016; Wolfson et al., 2019). In addition to rising rates of HZ at the overall population level, the incidence of HZ and frequency of complications such as postherpetic neuralgia are higher among immunocompromised subpopulations, per large insurance claims database studies in the US, UK, and Germany (Chen et al., 2014; Yanni et al., 2018; Schröder et al., 2017). Immunocompromised persons and other specific patient groups are at higher risk for severe varicella infections and complications (Table 1) (Centers for Disease Control and Prevention, 2015; Marin et al., 2013; Gnann, 2002; Moffat et al., 2007; Lamont et al., 2011; Bapat and Koren, 2013).
Varicella-zoster virus causes both varicella (chickenpox) and herpes zoster (shingles). Although varicella incidence has dramatically declined since introduction of the live-attenuated varicella vaccine, vaccination rates are suboptimal, and outbreaks still occur. Additionally, herpes zoster incidence continues to rise. Severe or fatal complications may result from varicella transmission to at-risk individuals who are exposed to either varicella or herpes zoster. An increasing number of children and adults are receiving immunosuppressive therapies and are at high risk for severe varicella and other complications if exposed to the virus. Clinical management of individuals exposed to varicella-zoster virus should take into consideration the type of exposure, evidence of immunity, and host-immune status with regard to ability to receive varicella vaccination safely. Post-exposure varicella vaccination may prevent infection or mitigate disease severity in persons eligible for vaccination. Post-exposure prophylaxis with varicella zoster immune globulin is indicated for populations ineligible for vaccination, including immunocompromised children and adults, pregnant women, newborns of mothers with varicella shortly before or after delivery, and premature infants. Appropriate post-exposure management of individuals exposed to either varicella or herpes zoster—including assessment of immune status and rapid provision of optimal prophylaxis—can help avoid potentially devastating complications of varicella-zoster virus infection.

View all citing articles on Scopus

View full text

Incidence of herpes zoster amongst adults varies by severity of immunosuppression

Highlights

Summary

Objectives

Methods

Results

Conclusions

Introduction

Section snippets

Data source

Study population

Incidence of herpes zoster

Discussion

Conclusions

Funding

Conflict of interest

Acknowledgements

J Clin Virol

J Infect

J Infect

Revue d'épidémiologie et de santé publique

J Clin Epidemiol

Epidemiology, outcome and control of varicella-zoster infection

Rev Med Microbiol

[Guidebook infectious diseases. Part 20: varicella, herpes zoster]

Varicella and herpes zoster. Part 1: virology, epidemiology, clinical picture, laboratory diagnostics

Med Klin

The epidemiology of herpes zoster in patients with newly diagnosed cancer

Cancer Epidemiol Biomarkers Prev

Complications of herpes zoster in cancer patients

Scand J Infect Dis

Risk of stroke after herpes zoster – evidence from a German self-controlled case-series study

PLoS One

Herpes zoster in Germany: quantifying the burden of disease

BMC Infect Dis

Epidemiology and cost of herpes zoster and postherpetic neuralgia in Germany

Eur J Health Econ

Systematic review of incidence and complications of herpes zoster: towards a global perspective

BMJ Open

The incidence of herpes zoster in a United States administrative database

J General Intern Med

Risk of herpes zoster among diabetics: a matched cohort study in a US insurance claim database before introduction of vaccination, 1997–2006

Infection

Incidence of herpes zoster in HIV-infected adults in the combined antiretroviral therapy era: results from the FHDH-ANRS CO4 cohort

Clin Infect Dis

Quantification of risk factors for herpes zoster: population based case-control study

BMJ